In many types of cancer, e.g., breast cancer, cells are released from the primary tumor and circulate in the blood stream until they lodge elsewhere in the body. The detection and identification of these circulating tumor cells (CNT's) is of major importance for an early diagnosis, for avoiding metastases, and for the follow-up of therapies. Early stage cancer detection is a milestone in cancer diagnosis and has triggered a plethora of studies with the aim to increase selectivity and reduce the limit of detection. To date, the available techniques for early cancer diagnosis using blood or liquid biopsies are often based on fluorescently-activated cell sorting (FACS, requiring fluorescent cell-labeling). This technique is time consuming and requires expensive instrumentation operated by specialized staff. Other techniques are also known.
One example of a technique that can be used is thermos rheology, as for example described by T. R. Kiessling in New Journal of Physics 15 (2013) art. No. 045026. The technique provides information on the mechanical properties of cells upon environmental changes but fluorescent labels are needed and it requires laborious optical imaging and data processing.
In another technique, use is made of fluorescence assisted cell sorting, as for example described by L. Bonetta in Nature Methods 2 (2005) 785-795. The technique has a high specificity and allows a very low detection limit, but fluorescent labels are required. In addition, cells need to be suspended such that information on tissue and cell-cell interactions are unavailable as well as the data processing is complicated due to the massive amounts of data that are obtained.
Yet another known technique for detecting certain types of cells is using a compact lens-free imaging flow cytometer, as for example described in Vercruysse et al. in Lab on a Chip 15 (2015) 1123-1132. In this setup, a lens-free imaging system is used for imaging cells in a flow cytometer. This technique is label-free, requires small volumes, is sensitive to cell morphology, and has the potential for further miniaturization. Nevertheless, using holographic images as is done in this technique results in a low resolution and the post analysis of the images is complex.
In addition, a method for identifying circulatory tumor cells (CTCs) in blood samples has been developed. This techniques, referred to as the CellSearch™ is described by Riethdorf, Sabine, et al., in Clinical Cancer Research 13.3 (2007): 920-928. The CellSearch™ uses protein-coated magnetic beads, which bind to cancer cells. The cells then are separated from the sample by applying a magnetic field to the mixture before being subjected to further analysis. This technique involves fluorescent staining the candidate cells and labelling the magnetic beads, thus, making the technique both laborious and expensive.
Also, molecular methods are used for the detection of cells, especially pathogens. These methods, reviewed in Law, Jodi Woan-Fei, et al in Frontiers in microbiology 5 (2015): 770 are based polymerase chain reactions oligonucleotide DNA microarrays, fluorescent in situ hybridization, and pyrosequencing. However, these techniques lack specificity and require target enrichment prior to detection. Unfortunately, common enrichment techniques suffer from cell loss, sample contamination and/or require laborious labelling steps. Moreover, these techniques are time inefficient and require highly skilled staff, as well as bulky and expensive instrumentation.
There is still a need for better methods and devices for characterizing or identifying bioparticles, such as for example cells or cell types.